Process for producing ribavirin

Abstract

There is disclosed a process for producing ribavirin from 1,2,4-triazole-carboxamide and a ribose donor by the enzymatic action of a microorganism belonging to specific genera, e.g. Brevebacterium. The specific feature of the invention is, above all, utilization of said microorganism under non-proliferatating conditions.

What is claimed is: 
     
       1. A process for producing ribavirin which comprises reacting 1,2,4-triazole-3-carboxamide or a salt thereof with a ribose donor selected from the group consisting of ribose-1-phosphates, nucleosides and nucleotides in the presence of an enzyme source based on a microorganism belonging to the species Brevibacterium acetylicum containing an enzyme which catalyzes the reaction to form ribavirin, said reaction taking place at a temperature of 40°-80° C., such that said microorganism is essentially non-proliferative, said reaction being carried out in an aqueous medium under conditions effective to and for a time sufficient to form ribavirin therein and recovering ribavirin formed from said medium. 
     
     
       2. A process according to claim 1, wherein the ribose donor is added separately to said enzymatic reaction system. 
     
     
       3. A process according to claim 1, wherein the ribose donor is present in said enzymatic reaction system as a component contained in the enzyme source employed or as a metabolite of the microorganism during the enzymatic reaction. 
     
     
       4. A process according to claim 1, wherein the microorganism employed is Brevibacterium acetylicum AT-6-7. 
     
     
       5. A process according to claim 1, wherein the enzyme source is selected from the group consisting of cultures of microorganisms, intact cells of microorganisms, and modifications of cells of microorganisms. 
     
     
       6. In a process for producing ribavirin from 1,2,4-triazole-3-carboxamide and a ribose donor in the presence of an enzyme source, the improvement comprising the use of an enzyme source capable of catalyzing the reaction between 1,2,4-triazole-3-carboxamide and a ribose donor, said enzyme source, being based on the microorganism of a species of Brevibacterium acetylicum. 
     
     
       7. A process as claimed in claim 6 in which the microorganism is Brevibacterium acetylicum AT-6-7 or a microorganism derived therefrom.